Neisseria meningitidis (meningococcus) is a Gram-negative spherical bacterium. Current meningococcal vaccines are also based on capsular saccharides. These include monovalent serogroup C conjugate vaccines and 4-valent conjugate mixtures for serogroups A, C, W135 and Y. There is currently no useful vaccine authorised for general use against serogroup B (‘MenB’).
One antigen which has been proposed for use in immunising against MenB is the factor H binding protein (‘fHbp’). This antigen has also been called protein ‘741’ (SEQ IDs 2535 & 2536 in ref 34), ‘NMB1870’, ‘GNA1870’ [refs. 1-3], ‘P2086’, ‘LP2086’ or ‘ORF2086’ [4-6]. The protein has been well studied. It is naturally a lipoprotein and is expressed across all meningococcal serogroups. The structure of fHbp's C-terminal immunodominant domain (‘fHbpC’) has been determined by NMR [7]. This part of the protein forms an eight-stranded β-barrel, whose strands are connected by loops of variable lengths. The barrel is preceded by a short α-helix and by a flexible N-terminal tail.
The fHbp antigen falls into three distinct variants or families [8] and it has been found that serum raised against a given family is bactericidal within the same family, but is not active against strains which express one of the other two families i.e. there is intra-family cross-protection, but not inter-family cross-protection. Thus reference 8 proposes to combine different variants of fHbp into a single vaccine composition, thereby increasing strain coverage, either as a mixture of separate proteins or as a fusion protein of the different variants (the latter being ‘tandem proteins’).